TY - JOUR
T1 - Total syntheses of glucosidase inhibitors, cyclophellitols
AU - Tatsuta, Kuniaki
AU - Niwata, Yoshihisa
AU - Umezawa, Kazuo
AU - Toshima, Kazunobu
AU - Nakata, Masaya
N1 - Funding Information:
We are grateful to the Institute of Microbial Chemistry for the generous support of our program, and also thank Pharmaceutical Research Laboratories, Meiji Seika Kaisha, Ltd. for an enzyme assay. Financial support by Ministry of Education, Science and Culture (Grant-in-Aid Scientific Research) is gratefully acknowledged.
PY - 1991/12/30
Y1 - 1991/12/30
N2 - A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.
AB - A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.
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U2 - 10.1016/0008-6215(91)89017-A
DO - 10.1016/0008-6215(91)89017-A
M3 - Article
AN - SCOPUS:0026332029
SN - 0008-6215
VL - 222
SP - 189
EP - 203
JO - Carbohydrate Research
JF - Carbohydrate Research
IS - C
ER -